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Abstract

Background

Our retrospective follow-up study aimed to explore the degree of overall mental distress
in a cohort of solid-organ transplantation (SOT) recipients after liver, heart or
lung transplantation. Furthermore, we investigated how overall mental distress is
linked to health-related quality of life.

Methods

123 SOT patients treated during the study period were enrolled in this investigation
at a mean of 24.6 months (SD=11.6) after transplantation. Before transplantation,
the Transplant Evaluation Rating Scale (TERS) was used to classify the level of adjustment
in psychosocial functioning among transplantation candidates. After transplantation,
recipients completed a research battery, which included the SCL-90-R, and the SF-36.

Transplantation recipients with overall mental distress had significant lower levels
of adjustment in psychosocial functioning before transaplantation than those without
overall mental distress as measured in the TERS. Transplantation-related overall mental
distress symptomatology was associated with maximal decrements in health-related quality
of life.

Conclusion

Transplantation recipients may face major transplantation- and treatment-related overall
mental distress and impairments to their health-related quality of life. Further,
overall mental distress is a high-risk factor in intensifying impairments to patients’
overall quality of life.

Keywords:

Background

Great achievements have been made in the field of transplantation surgery over the
past decades [1]. However, these usually life-saving interventions also present those affected with
stressful experiences and great demands that not infrequently also trigger consequent
psychiatric illnesses. Thus affective illnesses, maladjustment and severe anxiety
have been diagnosed in 19-54% of patients during psychiatric evaluation processes
[2-11].

In the assessment of outcomes following solid-organ transplantation, the transplantation’s
influence on psychic health and well-being is increasingly moving into the foreground
[1,7,12-17]. A number of outcome studies showed that solid-organ transplantation is associated
with improvements in health-related quality of life relative to the pretransplant
period, but without restoring the health status levels described in the general population
[10]. Earlier investigations showed a significant connection between psychiatric morbidity
and impaired health-related quality of life [3].

The transplantation itself and the intensive care unit stay might be traumatic stressors
that decrease health-related quality of life and can trigger overall mental distress.
The term overall mental distress is widely used by mental health practitioners, to
summarize a range of symptoms and experiences of a person's internal life that are
commonly held to be confusing, troubling, or out of the ordinary. Overall mental distress
has a wider scope than the related term mental illness. Thus mental illness refers
to a specific set of medically defined conditions. In contrast a person in overall
mental distress may display psychiatric symptoms such as depression, anxiety, confused
emotions, hallucination or rage, without necessarily actually being ill in a psychiatric
sense [18-20].

Aims of the study

Our retrospective follow-up study aimed to explore the degree of overall mental distress
in a cohort of solid-organ transplantation recipients after liver, heart or lung transplantation.
Furthermore, we investigated how overall mental distress is linked to health-related
quality of life. The well-validated Transplant Evaluation Rating Scale (TERS) [21] is well established to classify the level of adjustment in psychosocial functioning
among transplantation candidates. However, it is not proof of wheter pretransplant
evaluation based on the Transplant Evaluation Rating Scale can help in indicating
patients who are at high risk of posttransplant overall mental distress and impairments
in health-related quality of life. This research question is another research aim
of this study. Furthermore, factors that are described in the literature as potential
contributing or associated factors to overall mental distress and impairments in health-related
quality of life such as substance abuse (benzodiazepines, alcohol abuse), postoperative
medical complications, social support or medical complications are considered [10].

Method

Subjects and procedure

During the study period a total of 280 patients underwent transplantation at the Transplantation
Center of the Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.

Before transplantation, the psychometric observer-rating scale Transplant Evaluation
Rating Scale (TERS) [21] was used to classify the level of adjustment in psychosocial functioning among solid-organ
transplantation candidates. 65 of these 280 patients died before our retrospective
follow-up study started. 215 eligible transplantation recipients were contacted by
experienced psychiatrists and were asked to complete a research battery, which included
an author-compiled clinical questionnaire, the SCL-90-R [22,23] and the Medical Outcome Study Form (SF-36) [24]. 123 transplantation recipients returned the questionnaires, at a mean of 24.9 months
(SD=11.9) after transplantation. The SF-36 data were compared with data from normative
population whose individuals were drawn at random with respect to age and gender from
a large data base (n=3000) used for the validation of the SF-36 in Germany.

Psychometric tests

Before solid-organ transplantation the transplantation candidates were evaluated by
experienced consultation-liaison psychiatrists using the psychometric observer-rating
TERS [21].

The TERS scale classifies the level of adjustment in psychosocial functioning among
transplantation candidates and covers the different dimensions of psychosocial functions
(pre-existing psychiatric morbidity, substance abuse, compliance, coping strategies,
cognitive performance). The total sum reflects the current level of psychosocial functioning
of the particular transplantation candidate. The higher the score, the worse the current
level of psychosocial functioning.

After transplantation, an author-compiled questionnaire was used to obtain information
about the patient and transplantation characteristics. Demographic variables included
age, gender, years of education and/or vocational training, employment and marital
status at the time of psychiatric assessment. The patient’s employment status was
categorized as paid work (full- or part-time) or no paid work (disability, retired,
unemployed). Marital status was categorized as married, single, divorced, or widowed.
Further, preoperative chronic benzodiazepine consumption and preoperative alcohol
abuse were recorded.

The Symptom Check List (SCL-90-R) [22,23] is a well-researched and frequently used multidimensional self-rating 90-item scale
to screen for a broad range of psychological problems. Each of the 90 items is rated
on a five-point Likert scale ranging from “not at all” to “extremely” relating to
distress. The nine primary symptom dimensions are: Somatization, Obsessive-Compulsive,
Interpersonal Sensitivity, Depression, Anxiety, Anger-Hostility, Phobic Anxiety, Paranoid
Ideation and Psychoticism. The Global Severity Index is a global index that measures
overall mental distress and the cut-off T-value for clinically significant overall
mental distress is 60 [22].

To assess health-related quality of life, we applied the psychometrically well-validated
German translation of the Medical Outcome Study Form (SF-36) [24], a 36-item self-rating questionnaire that covers eight health-related domains. The
domains are Physical Functioning, Pain, General Health, Vitality, Social Functioning,
Mental Health, Role Physical, and, Role Emotional. The Role Physical is defined as
the extent to which the physical condition impairs work or other everyday activities
(e.g. achieving less than usual, limitation of types of activities, or difficulty
in carrying out certain activities). The Role Emotional is defined as the extent to
which emotional problems impair work or other everyday activities.

Each domain yields a score ranging from 0 to 100 (best). In the vast majority of the
published studies, the internal-consistency data of the SF-36 exceed 0.8 [24].

Statistical analyses

Descriptive statistics were produced based on demographic, treatment-related and psychometric
data (SCL-90-R, SF-36) and are presented as mean and standard deviation (SD) and median
and range. The psychometric data of the SF-36 scores were not normally distributed
as shown by the Kolmogorov-Smirnov Test. We therefore applied the non-parametric Mann–Whitney-U
test to test differences between patients with or without a high degree of overall
mental distress and the non-parametric Wilcoxon Test to compare transplantation recipients
without a high degree of overall mental distress with healthy controls matched by
age and gender. All statistic tests were two-tailed, with significance set at p<0.05.
In case of multiple comparisons, an alpha adjustment (Bonferroni) was used and p values
<0.006 were considered significant.

All statistical analyses were performed with SPSS 18.0 for Windows (SPSS; Chicago,
IL).

The study was approved by the Institutional Review Board of the Ludwig-Maximilians-University
of Munich. Data protection met the standards set by German law. All persons gave their
informed consent prior to their inclusion in the study.

Results

Sociodemographic characteristics

All 123 participants (69.1% men, 30.9% women) were Caucasian, and the mean age was
52.6 (SD=11.6; Median: 57.0) years.

Respondents with complete data were similar to those lost for refusal and untracebility
on the sociodemographic and treatment parameters.

Psychiatric morbidity before transplantation

Before transplantation the psychometric observer-rating scale TERS was performed on
all transplantation candidates, and the following psychiatric diagnoses were recorded:
alcoholism, abstinent at the time of psychiatric assessment (2.4%), alcohol abuse,
abstinent at the time of psychiatric assessment (7.4%), adjustment disorder (17.2%),
substance abuse (opiate, benzodiazepine) (4.9%), dysthymia (0.8%) and obsessive-compulsive
disorder (0.8%). These diagnoses have been based on a psychiatric clinical interview.

No significant differences between transplantation recipients with clinically significant
overall mental distress and those without were found in the following sociodemographic
characteristics: age (Mann–Whitney-U=1541.0; p=0.598), gender (χ2 =0.670; df=1, p=0.413), maritial status (χ2 =1.7; df=3, p=0.636), years in education and/or vocational training (Mann–Whitney-U=1562.5;
p=0.675). Regarding employment status, transplantation recipients with clinically
significant overall mental distress were less often employed than those without such
symptomatology (χ2 =9.9; df=1, p=0.04).

No significant differences between patients with postoperative overall mental distress
symptomatology and those without were found in the pre- and postoperative frequency
of alcohol abuse (Fisher’s exact test; p=0.585).

Transplantation recipients with overall mental distress more frequently take benzodiazepines
after the surgical intervention. However, it needs to be mentioned that even before
transplantation patients with postoperative overall mental distress symptomatology
displayed a higher level of benzodiazepine consumption (Fisher’s exact test; p<0.001).

Table 4 shows the benzodiazepine consumption before and after transplantation.

Overall mental distress and postoperative medical complications

In the sample we studied, the occurrence of postoperative medical complications (e.g.
bleeding, infections, cardio-vascular, rejection) did not significantly differ in
transplantation patients with postoperative overall mental distress from those without
overall mental distress (χ2 =3.202; df=1, p=0.074). Transplantation recipients with postoperative overall mental
distress did not show acute rejections following transplantation more frequently than
those without overall mental distress (Fisher’s exact test; p=0.330).

Overall mental distress and posttransplant type of medication

Patients with overall mental distress after transplantation did not differ at the
time of exploration in their prescribed medication from those recipients without postransplant
overall mental distress (tacrolimus, cyclosporine [χ2 =3.362; df=4; p=0.499]; steroids [χ2 =1.526; df=1; p=0.217]).

The level of adjustment in psychosocial functioning before transplantation and overall
mental distress after transplantation

Transplantation recipients with clinically significant overall mental distress had
significantly lower levels of adjustment in psychosocial functioning before transplantation
than those without significant overall mental distress after transplantation as measured
in the TERS (Mann–Whitney-U=1255; p=0.033). The mean TERS score before transplantation
was 36.4 (SD=9.8) in the subgroup of transplantation recipients with clinically significant
overall mental distress and 32.8 (SD=7.5) in transplantation recipients without significant
overall mental distress.

No differences between patients with clinically significant postoperative overall
mental distress symptomatology and those without were found in the preoperative frequency
of psychiatric disorders (Fisher’s exact test; p=0.237).

The level of adjustment in psychosocial functioning before transplantation and postoperative
medical complications and acute rejection

Transplantation recipients with postoperative medical complication did not differ
in the level of adjustment in psychosocial functioning before transplantation as measured
by the TERS (Mann–Whitney-U: 1614.5, p=0.160). However, transplant recipients with
acute rejection had significantly lower TERS scores before transplantation, than those
without rejection, indicating a lower level of adjustment in psychosocial functioning
before transplantation (pretransplant TERS mean score in the subgroup of recipients
with rejection: 33.28, pretransplant TERS mean score in the subgroup of recipients
without rejection: 36.68; Mann–Whitney-U: 593.5, p=0.027).

Health-related quality of life and overall mental distress after transplantation

In comparison with those transplantation recipients without clinically significant
overall mental distress, transplantation recipients suffering from overall mental
distress displayed significant impairments in all health-related quality of life SF-36
domains: Physical Functioning, Role Physical, Pain, General Health, Vitality, Social
Functioning, Role Emotional and Mental Health.

Table 8 shows the health-related quality of life SF-36 domains according to overall mental
distress.

The level of adjustment in psychosocial functioning before transplantation and health-related
quality of life after transplantation

A Spearman rank correlations between pretansplant TERS scores and postoperative quality
of life SF-36 domains scores showed that a low level of adjustment in psychosocial
functioning before transplantation (indicated by higher pretansplant TERS scores)
is significant negatively correlated with posttransplant health-related quality of
life in the following SF-36 domains: Vitality (rs=−0.239, p=0.009), Role Emotional (rs=−0.239, p=0.009), Social Functioning (rs=−0.182, p=0.046), and Mental Health (rs=−0.325, p<0.0001). In addition a trend of a negative correlation between high pretansplant
TERS scores and pottransplant low health-related quality of life was observed in the
SF-36 domains: Role emotional (rs=−0.176, p=0.055) and Pain (rs=−0.157, p=0.086). No significant correlations between pretansplant TERS scores and
pottransplant health-related quality of life were detected in the SF-36 domains Physical
Functioning (rs=−0.069, p=0.453) and General Health (rs=−0.131, p=0.153).

Discussion

Overall mental distress

In spite of great advances in transplantation surgery and constant improvement in
surgical techniques, tissue matching, organ preservation and patient selection, many
patients display symptoms of mental distress and psychiatric morbidity [1-4,6,8-10]. However, up to now there have only been a few empirical findings on the prevalence
of overall mental distress in transplantation recipients [25-27].

Obsessive-compulsive symptoms could be regarded as thoughts that are repeated reminders
of the transplantation and the subsequent stay in the intensive care unit. Concentration
difficulties and an impaired ability to work are also shown in this SCL-90-R dimension.
Furthermore, it could be hypothesized that the postransplant necessity for being very
accurate in taking the prescribed medication to avoid rejections may aggravate obsessive-compulsive
symptoms. Intrusive memories are also frequently mentioned in other studies as post-traumatic
symptoms after transplantation [28]. For example, in an orthotopic liver transplantation study by Rothenhäusler et al.
[10], 2.7% suffered from full post-traumatic stress disorder and 16% from partial posttraumatic
stress disorder. In another study by Favaro et al. [29], the estimated frequency of transplantation-related posttraumatic stress disorder
after heart transplantation was 12%.

Somatization symptoms could be interpreted on the one hand as greater body awareness
after transplantation, while on the other hand they could reflect increased self-monitoring
of the body due to traumatic illness and transplantation experiences.

Depressive and anxiety symptomatologies are a frequent finding after transplantation
and have been reported in numerous studies [4,6,8-10,13,30,31].

Deficits in interpersonal sensitivity (51.3%) as measured in the SCL-90-R subscale
interpersonal sensitivity are a less frequent finding in our study’s patients and
seem to show the physical vulnerability and insecurity remaining after the life-threatening
experiences of illness and transplantation. The physical impairments and resulting
feelings of low self-confidence could therefore cause of withdrawal from social life.
In the case of transplantation recipients the psychoticism subscale of the SCL-90-R
describes rather the isolation and the feeling of depersonalization after transplantation
and should not be primarily interpreted as measurement of psychotic symptoms. Such
symptoms are reported by 61.5%. Paranoid ideation (59%) in the SCL-90-R reflect the
sense of inferiority and mistrust after transplantation, and the primary symptom dimension
Anger and Hostility (53.8%) characterizes the irritability and unbalance in many transplantation
recipients.

Regarding our results it needs to be mentioned that transplantation candidates with
low levels of adjustment in psychosocial functioning before transplantation are at
higher risk of developing overall mental distress symptomatology after transplantation,
and the incidence of overall mental distress is independent of type of transplantation
and postoperative medical complications. However, transplant recipients with acute
rejection have significantly lower TERS scores before transplantation than those without
rejection, indicating a lower level of adjustment in psychosocial functioning before
transplantation. Furthermore, no significant differences between patients with postoperative
overall mental distress symptomatology and those without were found in the pre- and
postoperative frequency of alcohol abuse. However, transplantation recipients with
overall mental distress displayed a higher level of benzodiazepine consumption before
and after the surgical intervention.

Overall mental distress and health-related quality of life

Health-related quality of life is an important measure of outcome after transplantation
and in recent years, several studies have demonstrated that transplantation has beneficial
effects on quality of life for the majority of patients, both in intermediate and
in longterm outcomes [10,32,33]. However, impairments in health-related quality of life have been diagnosed in transplantation
recipients with some psychiatric disorders (e.g. anxiety and affective disorders,
posttraumatic stress disorder) after transplantation [25-28,33-35]. In this present study even transplantation recipients without overall mental distress
display more impairments in some health-related quality of life domains than healthy
controls matched by age and gender. It is recognised that overall mental distress
impairs health-related quality of life and life satisfaction even in people with overall
good health. Therefore a major aim of the present study was to explore if overall
mental distress in solid-organ transplantation recipients is strongly associated with
massive additional impairments to health-related quality of life. Indeed the transplantation
recipients with overall mental distress examined in this study had a lower health-related
quality of life compared with transplantation recipients without overall mental distress
as shown by impairments in all health-related quality of life SF-36 domains.

Furthermore, a low level of adjustment in psychosocial functioning before transplantation
(indicated by higher pretansplant TERS scores) was significantly negatively correlated
with posttransplant health-related quality of life in the SF-36 domains Vitality,
Role Emotional, Social Functioning, and Mental Health. In conclusion our results suggest
that overall mental distress in solid-organ transplantation recipients is strongly
associated with massive additional impairments to health-related quality of life.
These results allow for the hypotheses that overall mental distress has adverse health
effects that impair coping with activities in daily life, and/or that transplantation
recipients with overall mental distress symptoms already display greater health impairments
as such and not just after the transplantation.

Limitations

There are several limitations to our study. First, the format of the study is a retrospective
follow-up. Further, the small group sizes of the organ-subgroups may be a limitation
that needs to be mentioned. Regarding the statistical analysis the different organ-subgroups
have been considered as a whole group, in spite of their diverse characteristics (e.g.
development of organ insufficiency, different waiting times, different availability
of assisting devices). However, several studies have shown that a common data interpretation
is possible due to the homogeneously traumatic experiences caused by the solid-organ
transplantation followed by intensive care unit treatment [28]. All participating participants were Caucasian. As a limitation some ethnic groups
may have different interpretations of the symptoms.

Finally, our observations should be confirmed in studies with higher sample sizes
to gain a clearer insight into the degree of overall mental distress in transplantation
recipients.

Conclusions

Transplantation recipients may face major transplantation- and treatment-related overall
mental distress and impairments to their health-related quality of life. Further,
overall mental distress is a high-risk factor in intensifying impairments to patients’
overall quality of life.

The results of our study indicate that a pretransplant evaluation based on the Transplant
Evaluation Rating Scale can help in indicating patients who are at high risk of posttransplant
mental distress and impairments in health-related quality of life. Therefore pretransplant
diagnostic screening based on the Transplant Evaluation Rating Scale may facilitate
postransplant psychosocial support for these patients, who could be given specialized
help in advance of transplantation. Putatively this would also have an impact on the
transplant recipients’ postoperative health-related quality of life.

In conclusion we advise that as part of routine clinical care, an early and comprehensive
diagnosis and bio- and psychosocial therapeutic treatment of transplantation patients
with clinically significant concomitant overall mental distress to be carried out,
so that their overall mental distress symptomatology can be treated rapidly and their
quality of life can be improved. In the future the development of new specific therapeutic
strategies to reduce overall mental distress are desirable.

Abbreviations

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

AB: participated in data analysis; participated in the writing of the paper. TK: participated
in research design; participated in the performance of the research. H-BR: participated
in research design; participated in the performance of the research, participated
in the writing of the paper. All authors read and approved the final manuscript.

Saeed I, Rogers C, Murday A, Steering Group of the UK Cardiothoracic Transplant Audit: Health-related quality of life after cardiac transplantation: results of a UK National
Survey with Norm-based Comparisons.